So You Think You Have Tried Everything? Then Think Again- Part II

We will move on to treatments that are available in Tier II.  You don’t move on to Tier II until those things in Tier I have failed. This means that the supplements should have been tried for three months and the prevention medications mentioned in part I should have been tried at the therapeutic dose for at least a month.

Abortive / Symptomatic- Pharmacological  / Tier II

Rizatriptan (Maxalt®), naratriptan (Amerge®) I have saved these triptans for the second tier simply because the insurance companies require the patient to try sumatriptan first.  These two mentioned triptans are also generic.  It is important to emphasize that, while triptans are all of the same class, they are each unique. A patient may fail six of the seven triptans and the seventh one works perfectly. So it is worthwhile to keep trying. 


The difference between the two is that rizatriryptan tends to work faster but last shorter, while naratriptan works slower and lasts longer.  Naratriptan also has less side effects in general.



Same as sumatriptan. However, the side effects are less.

Eletriptan (Relpax®) / Zolmatriptan Nasal (Zomig®) Pros: In our opinion, this may be the most effective of all the triptans.  They are usually covered by insurances if the other triptans have been tried first.



These triptans do require insurance prior authorization.  The side effects with these triptans are in the middle of the spectrum.


Dihydroergotamine nasal spray (Migranal®) 


Pros:Dihydroergotamine, in many ways, is the perfect abortive medication.  It is highly effective, it is from a natural source (extracted from the ergot fungus), it has a very long duration and, unlike the triptans, it doesn’t cause rebound.



Dihydroergotamine doesn’t go through the stomach very well, so it needs to go into the blood stream through other routes.  I will mention the nasal spray at this juncture and the other forms later. The problem with the nasal spray is that the absorption is inconsistent and it can cause nasal stuffiness, which a lot of patients don’t like.  The other problem is that a few years ago, the price for the branded form went through the roof overnight. For that reason, most insurance companies stopped paying for it.  It is now available in a generic form but the coverage is still inconsistent.

Rescue Medications 

It is reasonable to consider “rescue” medication at the tier II level. These are primary prescription pain medications.  I will not list them by name because it would create too much confusion.


There are some people who cannot take the better, abortive medications due to medication conditions, or they have tried them all and they don’t work. In these cases, it is a humane choice to give the patient a pain medication as a second-line treatment.




Rescue medications have three major limitations:


1)      They only cover up the pain and do nothing about the underlying headache.


2)      All of them can cause rebound when they are used too often, such as more than two days per week. That is why it is a bad idea to prescribe only pain medications when someone has severe or frequent headaches.


3)      Most of them can cause addiction.  Sometimes nice people with headache disorders get inadvertently addicted to pain medication.  Then their whole situation becomes a nightmare.


Prevention-Nonpharmacological / Tier II

Trigger Avoidance At the tier II level, there are very few triggers left to look at because those should have been looked at during the tier I level.  I would add that if an MRI has not been done and if the headaches are daily or near daily, then it would be reasonable to do so at this juncture. 

Lab tests in headaches are basically useless and expensive.  We wish that they would reveal a single underlying trigger but they usually don’t. However, if it has not been done so far,  it would be worthwhile to do a TSH, blood count, Sed Rate and a few other basic tests to look for an underlying medical condition that could be triggering or worsening the headaches.


It is at this point that many patients want to try exotic diets.  They certainly can if they want. But to date, none of these so-called headache diets have proven to be beneficial even though they have been talked about for decades.


Supplements Like above, there are not many things to mention because supplements should have been used at the Tier I level.  I will only mention one because it is hard to find and the evidence supporting the use of it in general headaches is quite limited, and that is boswellia. It has been found to be effective in only one rare family of headaches referred to as the “indomethacin responsive headache syndromes.” It is taken around 250 MG three times per day. 
Procedures Because procedures are invasive, expensive, can have risks, and are permanent, you must approach them with caution.  The only procedure I will mention at this level would be the occipital nerve blocks. I would only consider them if the headaches start in the back of the head, where the occipital nerve is located.  Sometimes it can give lasting relief.  If the relief is only for a day or two, then it isn’t worth it.



Prevention – Pharmacological / Tier II

Anticonvulsants (seizure) medications General Review:Seizure medications can be highly effective in migraine prevention.  They are also about the only medications that we actually know how they work. In simple terms, they quieten overactive neurons by interfering with little channels that allow sodium, calcium and/or potassium in or out.  Their two biggest downfalls are that they are prone to nuisance side effects and the fact that many patients have a psychological aversion to the idea of taking seizure medications. I will mention three at this tier level.
Zonisamide (Zonegran®) Pros:Of all the 4-5 seizure medications used in migraine prevention, zonisamide is my favorite. It is my favorite because I think it has the least severe side effects.  While it never was FDA approved for migraine prevention (the company ran out of research money), four major studies were done showing that it is highly effective. It is one of a few medications that can cause weight loss (although minor) so many patients favor it for that reason.



The first major con is the fact that zonisamide does have a sulfa-related molecule in it.  The experts tell me that this should not be a reason to avoid it if you have a sulfa allergy.  The sulfa in antibiotics is very different.  However, when I prescribe it and then the pharmacist tells the patient that I made a mistake, it sews distrust. It does have some occasional side effects including nausea and sometimes cognitive side effects.

Topiramate (Topamax®) Pros:This is probably the most popular migraine prevention medication. It is FDA approved for migraine prevention and, therefore, covered well by insurance companies.  It may be one of the more effective migraine prevention medications, more so than zonisamide, but that isn’t clear. It’s believed superiority could just be hype. It can also cause more weight loss than zonisamide.



The readily available topiramate should be taken twice a day to get the most benefits. It does come in a once a day form, but it is not covered well by insurances.  Topiramate does have some nuisance side effects including tingling and cognitive problems (memory).

divalproex sodium (Depakote®) Pros:It was the second medication approved for migraine prevention more than 30 years ago. It is highly effective, not only in migraine but in other headache disorders as well.  It can be taken once a day and it is easy to check blood levels to see what the optimal dose is.  It is also a decent mood stabilizer, which can be helpful for patients with rapid mood shifts.



Divalproex, like the other seizure drugs, does have some side effects. The side effects with this medication tend to be GI related. For example, it can cause nausea, cramping and rarely, diarrhea. It also, just like Tylenol®, is processed through the liver and very rarely (1 in thousands) can cause liver irritations. It is easy to avoid those complications by doing a liver blood test.


New Antidepressants (SSRI / SNR)Venalfaxine (Effexor®, Effexor XR®) Pros:There is reasonable evidence supporting the use of venlafaxine to prevent headaches. Besides helping headaches, it has anti-depressant and anti-anxiety properties.



As with any medication, it can have side effects.  This type of medication has warnings about use with teenagers or children due to rare mood changes that have led to suicidal thoughts in very rare cases.